An iron-catalyzed oxidative coupling/cyclization reaction for the synthesis of benzoxazoles at room temperature is reported. This reaction was enabled by an inexpensive iron(iii) catalyst by treating readily available phenol derivatives with benzoyl aldehyde oximes. Mechanistic studies show that benzoyl aldehyde oxime is not only used as a substrate, but also serves as an ancillary ligand to support the iron salt in the promotion of the transformation.

The mechanism of action of naringin has been investigated in different models of experimentally induced cough in guinea pigs. In contrast to codeine phosphate (6 mg/kg, intravenous administration [i. v.]), naringin (15, 30, and 60 mg/kg, i. v.) had no central antitussive effect on cough elicited by electrical stimulation of the superior laryngeal nerve. Naringin (0.5, 1.0, and 2.0 µmol) could not prevent the cough reflex induced by stimulation of the trachea after intracerebroventricular injection (i. c. v.), while codeine phosphate (0.5 µmol) was highly effective. Further characterizing the peripheral mechanism of naringin, we found that its effect (50 mg/kg, i. v.) was not affected by the depletion of sensory neuropeptides, whereas levodropropizine (10 mg/kg, i. v.) lost its capacity to prevent cough in the capsaicin-desensitized guinea pig. Furthermore, pretreatment with glibenclamide (10 mg/kg, intraperitoneal [i. p.]) significantly reduced the antitussive effect of pinacidil (5 mg/kg, subcutaneous [s. c.]), but could not antagonize the antitussive effect of naringin (30 mg/kg, s. c.). Our present results suggest that naringin is not a central antitussive drug. And naringin does not exert its peripheral antitussive effect through either the sensory neuropeptides system or the modulation of ATP-sensitive K (+) channels.

OBJECTIVE Sporadic brain arteriovenous malformation (BAVM) is a tangled vascular lesion characterized by direct artery-to-vein connections that can cause life-threatening intracerebral hemorrhage (ICH). Recently, somatic mutations in KRAS have been reported in sporadic BAVM, and mutations in other mitogen-activated protein kinase (MAPK) signaling pathway genes have been identified in other vascular malformations. The objectives of this study were to systematically evaluate somatic mutations in MAPK pathway genes in patients with sporadic BAVM lesions and to evaluate the association of somatic mutations with phenotypes of sporadic BAVM severity. METHODS The authors performed whole-exome sequencing on paired lesion and blood DNA samples from 14 patients with sporadic BAVM, and 295 genes in the MAPK signaling pathway were evaluated to identify genes with somatic mutations in multiple patients with BAVM. Digital droplet polymerase chain reaction was used to validate KRAS G12V and G12D mutations and to assay an additional 56 BAVM samples. RESULTS The authors identified a total of 24 candidate BAVM-associated somatic variants in 11 MAPK pathway genes. The previously identified KRAS G12V and G12D mutations were the only recurrent mutations. Overall, somatic KRAS G12V was present in 14.5% of BAVM lesions and G12D was present in 31.9%. The authors did not detect a significant association between the presence or allelic burden of KRAS mutation and three BAVM phenotypes: lesion size (maximum diameter), age at diagnosis, and age at ICH. CONCLUSIONS The authors confirmed the high prevalence of somatic KRAS mutations in sporadic BAVM lesions and identified several candidate somatic variants in other MAPK pathway genes. These somatic variants may contribute to understanding of the etiology of sporadic BAVM and the clinical characteristics of patients with this condition.

An ovel iron-catalyzed direct alkylamination reactiono fp henols hasb een achieved with Obenzoyl-N-alkylhydroxylamines as aminating agents. This protocol provides af acile access to N-alkyl-substituteda minophenols though ar adical reactionf rom phenols.T he catalytic direct alkylamination operates at room temperature without the need of any ligands and additives to affordt he desired productsw ith excellentr egioselectivity and functional group tolerance. 1 HNMR (400 MHz, CDCl 3 ): d = 8.11 (s,1 H), 7.75 (d, J = 8.8 Hz, 1H), 7.72 (d, J = 8.4 Hz,1 H), 7.56 (d, J = 8.8 Hz, 1H), 7.34 (t, J = 8.4 Hz, 1H), 7.20 (t, J = 8.4 Hz, 1H), 7.18 (d, J = 8.8 Hz, 1H), 3.18-3.21 (m, 4H), 1.35-1.47 (m, 2H), 1.14-1.29 (m, 6H), 0.75-0.79 (m, 6H); 13 CNMR (100 MHz, CDCl 3 ): d = 153.

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